Breast Reconstruction Device and Methods

ABSTRACT

A novel human breast implant and method for using the same comprising a bioabsorbable implant into which native, autologous vascularized tissue and autologous fat is placed and propagated within a patient&#39;s chest as a breast implant.

RELATED APPLICATIONS

This continuation claims priority pursuant to 35 U.S.C. §120 to patentapplication Ser. No. 13/098,304, filed Apr. 29, 2011, a U.S.Non-Provisional Patent Application that claims priority to U.S.Provisional Application Ser. No. 61/329,496, filed Apr. 29, 2010,entitled Breast Reconstruction Device and Methods, and is related to thesubject matter of the Assignee's U.S. Pat. No. 7,846,728, entitledTissue Engineering In Vivo With Vascularized Scaffolds, filed Oct. 9,2007, which claims priority to U.S. Provisional Application Ser. No.60/851,686, entitled Tissue Engineering In Vivo With VascularizedScaffolds, filed Oct. 13, 2006, the contents of which are eachincorporated in their entirety herein.

FIELD OF THE INVENTION

The present invention relates to devices and related methods for organreconstruction and, more particularly, to devices and methods for thereconstruction of breasts.

BACKGROUND OF THE INVENTION

Breast cancer is the most common form of cancer and the second leadingcause of cancer deaths in American women. In 2009, approximately 194,280patients were estimated to be diagnosed with invasive breast cancer, andan estimated 40,610 will die of this disease (Jemal A., Siegel R., WardE., Hao Y., Xu J., and Thun M. J., Cancer statistics, 2009. CA Cancer JClin 2009; 59:225-49; the contents of which are herein incorporated byreference). Furthermore, 62,280 female carcinoma in situ breast caseswere diagnosed.

In 2008, according to the American Society of Plastic Surgeons, nearly79,500 women underwent breast reconstruction surgery post-mastectomy.Approximately 70% of these women had their breast(s) reconstructed withimplant(s) whereas the other 30% had autologous breast(s) reconstructedby one of the various flap procedures. Nearly 40% of the implantpatients experience severe capsular contracture within ten years. In2008, more than 14,000 procedures were performed in reconstructionpatients to remove the original implants. Complications in breastreconstruction are 2-3 fold higher than in breast augmentation. With amean follow-up of three years, 36% of breast reconstruction cases neededre-operation compared to 16% of cosmetic cases, versus 22% in revisionalcases (Handel N, Cordray T., Gutierrez J., and Hansen J. A., A long termstudy of outcomes, complications, and patient satisfaction with breastimplants, Plast Reconstr Surg 2006; 117:757-67; the contents of whichare herein incorporated by reference; the contents of which are hereinincorporated by reference). At six years in the Inamed Allergan study,reoperation is required in 52% of reconstruction, 28% in primaryaugmentation and 40% in revision augmentation (Spear S. L., Murphy D.K., Slicton A., Walker P. S. et al., Inamed silicone breast implant corestudy results at 6 years, Plast Reconstr Surg 2007; 120:8 S-16S; thecontents of which are herein incorporated by reference). The Mentorstudy showed a two-year rate of complication or reoperation of 43% forprimary reconstruction, 42% for revision reconstruction, versus 25% forprimary augmentation and 30% for revision augmentation (Cunningham B.,The Mentor study on contour profile gel silicone Memory Gel breastimplants. Plast Reconstr Surg 2007; 120:33 S-9S; the contents of whichare herein incorporated by reference).

Autologous tissue transfer represents a second option for breastreconstruction after mastectomy. The techniques involve free TRAM(transverse rectus abdominis musculocutaneous) flaps, pedicled TRAM,free DIEP (deep inferior epigastric perforator) flaps, pedicledlatissimus dorsi myocutaneous flaps, and gluteal flaps. These operationstake several hours; require a hospital stay of approximately 4-5 daysand subsequent outpatient rehabilitation of approximately 4-6 weeks. Thepatient then has one or more permanent large scars at the donor site(s).One representative study reports a complication rate of 46%, with 5%total flap loss and 4% partial flap loss (Sullivan S. R., Fletcher D. R.D., Isom C. D., Isik F. F., True incidence of all complicationsfollowing immediate and delayed breast reconstruction. Plast ReconstrSurg 2008; 122:19-28; the contents of which are herein incorporated byreference). Another recent report showed a complication rate of 27% forTRAM flaps and 68% for latissimus flaps (Spear S. L., Newman M. K.,Bedford M. S., Schwartz K. A., Cohen M., and Schwartz J. S., Aretrospective analysis of outcomes using three common methods forimmediate breast reconstruction. Plast Reconstr Surg 2008; 122:340-7;the contents of which are herein incorporated by reference).

In patients who need radiation, complications are quite common (JhaveriJ. D., Rush S. C., Kostroff K., Derisi D., Farber L. A., Maurer V. E.,Bosworth J. L., Clinical Outcomes of Postmastectomy Radiation Therapyafter Immediate Breast Reconstruction. Int J Radiat Oncol Biol Phys2008; 72:859-65; the contents of which are herein incorporated byreference). Complications in this study were scored as follows: Grade 1(no discomfort), grade 2 (discomfort affecting activities of dailyliving), grade 3 (surgical interventions or intravenous antibioticsrequired), and grade 4 (removal or replacement of the reconstruction).The overall rate of severe complications (grade 3-4) was 25%, andrate-of poor functional results was 43%. Acceptable cosmesis wasreported by 51% of patients reconstructed with implants and 83% of thosereconstructed with autologous tissue reconstruction.

Capsular Contracture

The commercial manufacture of breast implants has existed for over 50years. Despite many design innovations including foam implants, siliconeshells, many different filler materials, foam coating, textured coating,and cohesive gels, capsular contracture still continues to be the mostcommon complication associated with breast implants. No new designinnovation on the horizon has shown any promise to prevent thiscomplication from occurring in some patients. The fundamental problemappears to be caused by a nonspecific inflammatory response to a foreignbody introduced into human tissue. The Baker classification hascontinued as the most common standard method to describe contracture(Spear S. L., Baker J. L., Classification of capsular contracture afterprosthetic breast reconstruction. Plast Reconstr Surg 1995; 96:1119-23;the contents of which are herein incorporated by reference). Thisclassification rates a breast as follows: Class I—the augmented breastfeels as soft as an unoperated one; Class II—the breast is less soft,and the implant can be palpated but it is not visible; Class III—thebreast is more firm, the implant can be palpated easily, and it (ordistortion from it) can be seen; and Class IV—the breast is firm, hard,tender, painful, cold, and distortion is often marked. Class I and IIbreasts are considered clinically satisfactory. Class III and IV areconsidered serious.

The Mentor study with 3-year follow up showed a serious capsularcontracture rate of 11% for augmentation and 13% for reconstruction. TheInamed study on silicone implants with data available at six yearsrevealed serious contracture in 16% of reconstruction cases, 15% ofcosmetic cases, and 21% in revision augmentation (Spear S. L., Murphy D.K., Slicton A., Walker P. S. et al., Inamed silicone breast implant corestudy results at 6 years. Plast Reconstr Surg 2007; 120:8 S-16S; thecontents of which are herein incorporated by reference). A 10-year studyshows contracture rate of 22% for augmentation and 38% forreconstruction, and 42% for revision cases (Handel N., Cordray T.,Gutierrez J., and Hansen J. A., A long term study of outcomes,complications, and patient satisfaction with breast implants. PlastReconstr Surg 2006; 117:757-67; the contents of which are hereinincorporated by reference). Contracture is the most common culprit,accounting for 56% of cases that need re-operation. Reporting on aseries of 186 implants, Peters et al. observed that Class III-IVcontractures continue to accumulate over time, reaching 100% aroundsilicone gel-filled implants at 25 years (Peters W., Smith D., FornasierV., Lugowski S., Ibanez D., An outcome analysis of 100 women afterexplantation of silicone gel breast implants. Ann Plast Surg 1997;39(1):9-19).

Serious capsular contractures require frequent operative interventionssuch as open capsulotomy, explantation or replacement with new implants.Unfortunately, as seen in the above statistics, revision augmentationcases will have an even higher rate of eventual contractures. Subsequentsurgeries will be more difficult, and in many cases will requireautologous tissue flaps to preserve the patient's breasts.

Non-Surgical Breast Augmentation

The BRAVA Breast Enhancement and Shaping System is an external tissueexpander that is sold on the internet directly to consumers without FDAapproval (www.brava.com). The mechanical device is shaped like a bra.Once worn, the system applies a gentle three-dimensional pull, whichplaces the breast under tension. The tension exerted is approximately 15to 30 mmHg, resulting in fuller breasts over time. The bra should beworn for at least 10 hours a day every day. Side effects include rash,swelling, discomfort, dermatitis, allergic reaction, hyperpigmentation,and costochondritis. A recent study showed that breast enlargementwithout surgery is possible with this external tissue expander inhealthy women with intact breasts without any active breast disease(Schlenz I, Kaider A., The Brava external tissue expander: Is breastenlargement without surgery a reality? Plast Reconstr Surg 2007;120:1680-9; the contents of which are herein incorporated by reference).Noncompliant subjects were excluded from analysis. The 40 compliantwomen used Brava 11 hours a day for a median period of 18.5 weeks(range, 14 to 52 weeks). The median volume increase was 155 cc (range,95 to 300 cc). It is difficult to envision that this device would workon post-mastectomy cases, because there is only skin left without breastin the setting of adjuvant cancer treatments that inhibit new tissue andblood vessel formation.

Fat Grafting Breast Reconstruction

Surgeons have attempted direct autologous fat grafting into the breastfor decades (Coleman S. R., Saboeiro A. P., Fat grafting to the breastrevisited: safety and efficacy. Plast Reconstr Surg 2007; 119:775-85;the contents of which are herein incorporated by reference). However,tissue resorption often occurs when non-vascularized grafts aretransferred in human autograft transplantation. All human autograftsundergo this resorption even in the absence of infection,antigen-antibody mismatch, or lack of nutrition. A list of the tissueswhich have been autografted with well documented resorption over timeincludes fat grafts. Fat grafts larger than a few mm in diameter arewell documented of undergoing resorption over time. Except for smallvolume fat grafting transferred into multiple well vascularized tunnels,most fat grafts undergo partial resorption.

The most disconcerting aspect is that the resorption rate varies widelyfrom 20 to 90 percent. This makes it difficult to compensate forresorption by overgrafting with larger volumes. When fat is transferredby autologous non-vascularized grafting, by pedicled flaps, or by freemicrovascular flap transfer, fat necrosis is a minor occurrence withmajor consequences. Even if only a small percentage of the fat cellsundergo cell death, these dead cells undergo saponification releasingabundant long chain fatty acids from the disrupted plasma membrane.Precipitation of these long chain fatty acids with calcium results inpalpable masses that appear on mammography to be microcalcifications.

This artifact makes cancer surveillance difficult with mammography. As aconsequence, fat grafting for breast augmentation may make future cancerdetection difficult. For this reason, autologous fat grafting forcosmetic breast augmentation has been discouraged by the FDA,radiological societies, and the plastic surgery community. Fat necrosisalso causes concerns when it occurs in the reconstructed breast. In thisscenario, both patients and their oncologists worry that the palpablefat necrosis may be recurrent cancer. This often necessitates a biopsyto rule out this possibility. Fat grafting certainly does not produceenough volume to make an entire breast, therefore it is not a viableoption for breast reconstruction.

Fat Stem Cell Breast Reconstruction

Regenerative medicine is a rapidly expanding set of innovative medicaltechnologies that restore function by enabling the body to repair,replace, and regenerate damaged, aging or diseased cells, tissues andorgans. There is much interest in the use of both adult and embryonicstem cells. Human adult stem cells have been successfully isolated fromliposuction fat (Zuk P A, Zhu M, Ashjian P, et al., Human adipose tissueis a source of multipotent stem cells. Mol Biol Cell 2002; 13:4279-95;the contents of which are herein incorporated by reference).

Several commercial ventures hope to use this fat for breastreconstruction. Cytori Therapeutics developed the Cell-EnhancedReconstruction, which is a procedure whereby a patient's fat tissue isenriched with his or her own adipose-derived stem and regenerative cellsto create a natural filler. Clinical trials are being conducted inEurope in women who underwent lumpectomies for breast cancer. It isdifficult to envision that this and similar procedures would effectivelyprovide enough volume to replace one or two entire breasts, as neededfor mastectomy cases. Injectable scaffolds are promising substrates forregenerative medicine applications. In a recent study, humanadipose-derived stem cells were mixed with multiarm amino-terminatedpoly(ethylene glycol) (PEG) hydrogels that were crosslinked withgenipin, a compound naturally derived from the gardenia fruit (Tan H,Defail A J, Rubin J P, Chu C R, Marra K G., Novel multiarm PEG-basedhydrogels for tissue engineering. J Biomed Mater Res A 2009; Epub March16; the contents of which are herein incorporated by reference). Anothermaterial used with stem cells includes porous collagenous microbeads.

Two-Dimensional Meshes and Scaffolds

There are several FDA-approved synthetic bioabsorbable meshes on themarket. These are sold as flat sheets of varying sizes, and areindicated for temporary wound or organ support. One example is thecommonly used Vicryl mesh made of glycolic and lactic acids (Ethicon).The synthetic materials have been shown to be inert, nonantigenic,nonpyrogenic, and to elicit only a mild tissue reaction duringabsorption. The knitted mesh has an initial average burst strength ofapproximately 63 pounds prior to implantation in rats, and retains 80percent of this strength after 14 days in vivo. Subcutaneousimplantation studies in rats indicate that the absorption of Vicryl meshis minimal until about six weeks, and is essentially complete between 60and 90 days. Another commonly used mesh is the Dexon brand from U.S.Surgical Corporation. It is constructed from only polyglycolic acid, isinert, nonantigenic, noncollagenous, and does not enhance any secondaryinfection. For plating, surgeons often use Lactosorb made out ofglycolic and lactic acids (Biomet). At initial placement, its strengthis comparable to that of titanium plating, and it retains 80 percent ofthis strength at eight weeks. It is degraded in the human body byhydrolysis completely by one year. Lactosorb is available in a varietyof plate shapes and different screw sizes.

AlloDerm (Life Cell) is an acellular dermal matrix derived from donatedhuman skin tissue supplied by US tissue banks. This natural frameworkconsists of proteins with a structurally intact basement membrane,intact collagen fibers and bundles to support tissue ingrowth, intactelastin filaments for biomechanical integrity, and hyaluronan andproteoglycans. Dermagraft (Advanced BioHealing) is manufactured fromhuman fibroblast cells derived from newborn foreskin. These fibroblastsare placed on a bioabsorbable polyglactin mesh. Non-human derived dermalmatrix products are also available. For example, Strattice (Life Cell)is derived from porcine dermis and undergoes processing to removes cellsand reduce the key component believed to play a major role in thexenogeneic rejection response. Another porcine product is XenMatriX fromBrennen Medical.

In general, these two-dimensional meshes and scaffolds are used asadjuncts in breast reconstruction. For example, AlloDerm is sometimesused in implant reconstruction to help enclose the subpectoral pocketand prevent the implant from displacement (Zienowicz R J, Karacaoglu E.Implant-based breast reconstruction with allograft. Plast Reconstr Surg2007; 120:373-81; the contents of which are herein incorporated byreference). Surgeons may also use bioabsorbable synthetic mesh for thesame purpose in the breast and for repair of hernias in flap donorsites.

Three-Dimensional Scaffolds

Scaffold technology has made multilayer tissue engineering possible aswell, with multi-cell structures successfully grown in the laboratory.Despite these successes, major roadblocks still exist in translationalresearch. As a consequence, the only human vascular organ successfullyengineered to date is a urinary bladder (Atala A., Bauer S. B., SokerS., Yoo J. J., Retik A. B., Tissue-engineered autologous bladders forpatients needing cystoplasty. Lancet 2006; 367:1241-6; the contents ofwhich are herein incorporated by reference). Almost all tissueengineering thus far is done with non-vascularized scaffolds. Althoughneovascularization with capillaries occurs very reliably in scaffolds ofabout 1 millimeter in thickness, most human organs are much larger thanthis. As a consequence, tissue engineering on scaffolds is limited insize by the lack of arterial and venous structures which do not grow aswell as capillaries. In summary, vascular supply limits organ size inscaffold based tissue engineering.

There has been extensive research by others to develop biocompatiblecomposites/scaffolds. For example, U.S. Publication No. 2002/0022883 toBurg (The contents of which are herein incorporated by reference)described a biocompatible composite with viscous fluid for injectioninto defects. Of course, this concept would not work for organogenesis.U.S. Publication No. 20040126405 to Sahatjian et al. (The contents ofwhich are herein incorporated by reference) proposed a three dimensionalcell scaffold either as a sheet or a tube configured into variousshapes. U.S. Pat. No. 5,716,404 to Vacanti et al. (The contents of whichare herein incorporated by reference) proposed placing dissociated cellsinto a biodegradable matrix to be implanted with a tissue expanderdevice into the breast. However, cells would perish without new bloodvessels, and this idea did not materialize into practical use since itsissued patent in 1998. U.S. Pat. Nos. 5,804,1784, 5,770,193, and5,759,830 to Vacanti et al. (The contents of which are hereinincorporated by reference) also reported the idea of implanting sheetsof cell-matrix structure adjacent to mesentery, omentum, or peritoneumtissue.

U.S. Publication No. 2002/0119180 to Yelick et al. (The contents ofwhich are herein incorporated by reference) successfully constructed abiodegradable polymer scaffold molded in the shape of a tooth and placedit onto the omentum of rats. U.S. Publication No. 20030129751 toGrikscheit et al. (The contents of which are herein incorporated byreference) describes a method to achieve high density seeding of polymerscaffold with organoid units. The disclosed scaffolds arecollagen-coated 1 centimeter long 0.5 millimeters woven polyglycolicacid tubes with a diameter of 0.5 centimeter, that are sutured to therat's omentum to make new colonic tissue (Grikscheit T. C., Ochoa E. R.,Ramsanahie A., Alsberg E., Mooney D., Whang E. E., Vacanti J. P.,Tissue-engineered large intestine resembles native colon withappropriate in vitro physiology and architecture. Ann. Surg. 2003;238:35-41; the contents of which are herein incorporated by reference).

The Morrison group from Australia developed a vascularized chambercomprising of an empty box which is buried subcutaneously into ananimal. An arteriovenous blood leash, either as a ligated pedicle or asan arteriovenous fistulous loop fashioned from the inferior epigastricor femoral vessels into the groin by microsurgical techniques, is insetinto the chamber through a small side hole. This sealed ischemic chamberspace that cannot close spontaneously promotes an intense and prolongedangiogenic response, and the chamber box fills with granulation tissue.This over time creates a vascularized flap of tissue that can betransplanted to a site of need as a free flap for repair of wound. Inthe pig, the surgeons included a small amount of autologous living fatinto the chamber. Subsequently, 80 milliliters chambers would becomefilled with tissue of which approximately 50 percent is new fat(Morrison W. A., Progress in tissue engineering of soft tissue andorgans. Surgery 2009; 145:127-30; the contents of which are hereinincorporated by reference).

In the case of breast reconstruction, immediate reconstruction aftermastectomy is a particularly challenging situation for tissueengineering. Almost all women who undergo mastectomy(ies) for breastcancer will need adjuvant systemic therapy shortly afterwards.Chemotherapy reliably suppresses wound vascularization, and anti-hormonedrugs such as tamoxifen have been shown to inhibit angiogenesis.Furthermore, a significant number of post-mastectomy patients also needpostoperative radiation to the chest and therefore the new “breast.”Radiation effectively eliminates any hope for robustneo-vascularization, not just for the moment but for the rest of thepatient's life.

Utilization of the Omentum

The omentum, shown in FIG. 1, has been used by various investigators asa source of vasculature for tissue engineering purposes: porcine tooth(Sumita Y, Honda M J, Ohara T., Tsuchiya S., Sagara H., Kagami H., andUeda M. Performance of collagen sponge as a 3-D scaffold fortooth-tissue engineering. Biomaterials 2006; 27:3238-48; the contents ofwhich are herein incorporated by reference), dog small intestine (HoriY, Nakamura T., Matsumoto K., Kurokawa Y., Satomi S., Shimizu Y., Tissueengineering of the small intestine by acellular collagen sponge scaffoldgrafting. Int. J. Artif. Organs. 2001; 24:50-4; the contents of whichare herein incorporated by reference), dog tracheal defects (Kim J., SuhS. W., Shin J. Y., Kim J. H., Choi Y. S., Kim H., Replacement of atracheal defect with a tissue-engineered prosthesis: early results fromanimal experiments. J. Thorac. Cardiovasc. Surg. 2004; 128:124-9; thecontents of which are herein incorporated by reference), canine oralepithelial cells and rib chondrocytes (Suh et al., 2004), and porcinebladder urothelial cells (Moriya K., Kakizaki H., Murakumo M., WatanabeS., Chen Q., Nonomura K., Koyanagi T., Creation of luminal tissuecovered with urothelium by implantation of cultured urothelial cellsinto the peritoneal cavity. J Urol. 2003; 170:2480-5; the contents ofwhich are herein incorporated by reference).

Recently, a successful human clinical trial has been reported (Atala A.,Bauer S. B., Soker S., Yoo J. J., Retik A. B., Tissue-engineeredautologous bladders for patients needing cystoplasty. Lancet 2006;367:1241-6; and U.S. Publication No. 2007/0059293 to Atala; the contentsof which are herein incorporated by reference). Autologous bladder cellswere seeded on a biodegradable bladder-shaped scaffold made of collagenand polyglycolic acid, which was then implanted covered with omentuminto the patients with myelomeningocele. In all of the above studies,the omentum was used as a single layer attached to one side of a flatscaffold, or wrapped around a three-dimensional scaffold.

The Vacanti group also used the mesentery and interscapular fat pad togrow hepatocytes, intestinal cells and pancreatic islet cells in miceand rats (Vacanti J. P., Morse M. A., Saltzman W. M., Domb A. J.,Perez-Atayde A., and Langer R., Selective cell transplantation usingbioabsorbable artificial polymers as matrices. J. Pediatr. Surg. 1988;23:3-9; the contents of which are herein incorporated by reference).

In clinical practice, the omentum flaps have been used most commonly forchest wall reconstruction after sternal dehiscence. Omental flaps haverarely been harvested laparoscopically for direct breast reconstruction(Zaha H., Inamine S., Naito T., and Nomura H., Laparoscopicallyharvested omental flap for immediate breast reconstruction. Am J Surg2006; 192:556-8; the contents of which are herein incorporated byreference). To allow passage of the omentum, a subcutaneous tunnel wasmade from the medial end of the inframammary fold to the xiphoidprocess. The omentum was stapled to the pectoralis major muscle and thenmanually shaped into a mound. The mastectomy skin was then closed.Unlike TRAM or DIEP flaps, the omental flap method leaves minimal scarsfrom the harvesting procedure. The operative time is shorter than withtraditional TRAM and DIEP flaps. Hospital stay would be much shorter,potentially just overnight, because the patient does not need to recoverfrom extensive musculocutaneous dissection and/or close monitoringrequired for free flaps.

However, some major disadvantages have prevented omental flaps from wideclinical acceptance. The shape of the resulting reconstructed breast canwidely vary due to lack of structural support. The size of the omentumis variable in individuals, and there is no reliable method prior tosurgery to accurately estimate its size. Usually, the omentum is toosmall to adequately reconstruct both breasts and sometimes is too smallto reconstruct even only one breast. Interestingly, an implant placed inthis situation surrounded by omentum has a much less likelihood ofdeveloping contracture (Cothier-Savay I., Tamtawi B., Dohnt F., RauloY., Baruch J., Immediate breast reconstruction using a laparoscopicallyharvested omental flap. Plast Reconstr Surg 2001; 107:1156-63; thecontents of which are herein incorporated by reference).

What is needed in the art is a breast implant that overcomes the abovedescribed shortcomings of the prior art.

OBJECTS AND SUMMARY OF THE INVENTION

The present invention is a novel human breast implant and method forusing the same that addresses many of the shortcomings of the prior artimplants by providing a bioabsorbable implant into which autologousvascularized tissue and autologous fat is placed within the patient inorder to propagate vascularized tissue that is subsequently transferredto the patient's breast as a breast implant.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects, features and advantages of which embodiments ofthe invention are capable of will be apparent and elucidated from thefollowing description of embodiments of the present invention, referencebeing made to the accompanying drawings, in which

FIG. 1 is a perspective view of an omentum.

FIG. 2 is a side elevation view of an implant according to oneembodiment of the present invention.

FIG. 3A is a plan view of an implant according to one embodiment of thepresent invention.

FIG. 3B is a perspective view of an implant according to one embodimentof the present invention.

FIG. 4 is a perspective view of a base of an implant according to oneembodiment of the present invention.

FIG. 5 is a perspective view of a body of an implant according to oneembodiment of the present invention.

FIG. 6 is a partial cut-away view of an implant according to oneembodiment of the present invention.

FIG. 7 is a plan view of a body of an implant according to oneembodiment of the present invention.

FIG. 8 is a side elevation view of a body of an implant according to oneembodiment of the present invention.

FIG. 9A is a side elevation view of a body of an implant according toone embodiment of the present invention.

FIG. 9B is a side elevation view of a body of an implant according toone embodiment of the present invention.

FIG. 10 is a perspective view of a body of an implant according to oneembodiment of the present invention.

FIG. 11 is a side elevation view of a base of an implant according toone embodiment of the present invention.

FIG. 12 is a plan view of a base of an implant according to oneembodiment of the present invention.

FIG. 13 is a perspective view of a base of an implant according to oneembodiment of the present invention.

FIG. 14 is a cut-away side elevation view according to one embodiment ofthe present invention.

FIG. 15 is a partial transparent perspective view of an implantaccording to one embodiment of the present invention.

FIG. 16 is a perspective view of a base of an implant according to oneembodiment of the present invention.

FIG. 17 is a partial transparent perspective view of an implantaccording to one embodiment of the present invention.

FIG. 18 is a perspective view of a base of an implant according to oneembodiment of the present invention.

FIG. 19 is a side elevation view of a base of an implant according toone embodiment of the present invention.

FIG. 20 is a side elevation view of a base of an implant according toone embodiment of the present invention.

FIG. 21 is a chemical formula of a co-polymer employed in an implantaccording to one embodiment of the present invention.

FIG. 22 is a perspective view of the finite element analysis mesh of abody of an implant according to one embodiment of the present invention.

FIG. 23 is a perspective view of the finite element analysis of a bodyof an implant according to one embodiment of the present invention.

FIG. 24 is a flow diagram of a method for using an implant according toone embodiment of the present invention.

FIG. 25 is a photograph of a 20× magnification of a portion of a stainedslide of vascularized rat fat produced according to one embodiment ofthe present invention.

FIG. 26 is a photograph of a 100× magnification of a portion of astained slide of vascularized rat fat produced according to oneembodiment of the present invention.

FIG. 27 is a photograph of an x-ray of an implant removed from a pigthat was produced according to one embodiment of the present invention.

FIG. 28 is a photograph of a portion of fat produced in a pig accordingto one embodiment of the present invention.

FIG. 29 is a photograph of a magnification of a portion of a stainedslide of vascularized pig fat produced according to one embodiment ofthe present invention.

DESCRIPTION OF EMBODIMENTS

Specific embodiments of the invention will now be described withreference to the accompanying drawings. This invention may, however, beembodied in many different forms and should not be construed as limitedto the embodiments set forth herein; rather, these embodiments areprovided so that this disclosure will be thorough and complete, and willfully convey the scope of the invention to those skilled in the art. Theterminology used in the detailed description of the embodimentsillustrated in the accompanying drawings is not intended to be limitingof the invention. In the drawings, like numbers refer to like elements.

The present invention represents a novel solution for organreconstruction and, specifically, for breast reconstruction that isbased, in part, on a bioabsorbable implant scaffold. Broadly speaking,the device of the present invention employs a bioabsorbable scaffoldingwhich houses an autologous, natively vascularized tissue and anautologous, fat tissue matrix. For example, the bioabsorbable scaffoldmay include an outer shell formed in the shape of a breast. Theautologous, natively vascularized tissue may, for example, include atleast a portion of the omentum.

The device and associated methods of use of the present inventionprovide numerous advantages over current devices and methods for breastreconstruction. For example, the bioabsorbable scaffold of the presentinvention is tissue-based without a permanent foreign body therebyavoiding the associated high complications and re-operation ratedescribed above for typical implants. The operative time for employingthe bioabsorbable scaffold of the present invention is a few hours,shorter than traditional flap reconstruction, and blood loss issignificantly less, thus stress to the patient's body is minimized. Thepostoperative monitor requirements after employing the bioabsorbablescaffold of the present invention are less intensive than that for freeflaps. Furthermore, the hospital stay length is similar to implantreconstruction, 1-2 days, versus 4-6 days required for traditional flapreconstruction. Finally, because there is no permanent muscle loss, nolarge scars and potential defects at the flap donor site(s),rehabilitation subsequent to employing the bioabsorbable scaffold of thepresent invention is anticipated to be many weeks less than traditionalflap reconstruction.

In order to overcome the limitations of organ size in scaffold-basedtissue engineering due to limited vascular supply, the present inventionemploys a vascularized scaffold having a complete vascular bed 5.Preferably, an autologous, natively vascularized tissue provides thisvascular bed 5. The vascular bed 5 ideally comprises at least one largeinflow artery of, for example, approximately 2-3 millimeters and atleast one large outflow vein of, for example, approximately 3-4millimeters connected to a native circulatory network.

In one embodiment of the present invention, the omentum, shown in FIG.1, is employed for the vascular bed. The omentum contains its own richvascular supply, both arterial and venous, throughout its structure. Thelarge arteries branch into hundreds of arterioles and capillaries, thelarge veins into hundreds of venules. These vessels interdigitate andinterconnect in a complex three-dimension network.

An omentum-based vascularized growth chamber has significant promise formany translational research applications. Rationale for this optimismincludes the following reasons. First, the omentum is a naturallyoccurring, expendable vascular scaffold that has been shown to develop arich capillary network. Despite the fact that it is only fat, lymphaticsand blood vessels, it has been used to revascularize ischemic areas,treat lymphedema, and cover the heart after sternal debridements.Second, the omentum has a dual blood supply. This means that it can besplit into two separate sections thereby allowing for develop twovascularized growth chambers in the extra-peritoneal space. This wouldmake it ideal for breast reconstruction tissue engineering, since twobreasts could be made. In this model, the omentum retrieval could bedone using laparoscopic techniques. Then, the growth chamber would beinserted under the breast skin and above the pectoralis muscle.

In certain other embodiments, the device of the present inventionemploys sources of vascular bed 5 other than the omentum. For example,in one embodiment, a partial rectus abdominis muscle may be employed forthe vascular bed 5. In this embodiment, a small incision is made toharvest a small amount of the muscle, instead of the entire muscle inthe traditional TRAM (transverse rectus abdominis musculocutaneous) flapprocedure. Other contemplated sources for the vascular bed 5 include,but are not limited to, a partial, or entire, latissimus muscle; apartial, or entire, external oblique muscle; and a partial, or entire,serratus anterior muscle.

With respect to the non-biological structure or scaffold of the presentinvention, the outer shape of the bioabsorbable scaffold is designed toresemble that of a human breast. The scaffold interior is configured toaccommodate multiple layers or folds of the vascular bed 5, for examplemultiple folds of an omentum that is placed within the scaffold incontact with an autologous fat tissue matrix.

With reference to FIGS. 2-6, in one embodiment of the present invention,a bioabsorbable implant 10 includes a bowl-shaped body 12 and a base 14.The implant 10 may, for example have a volume of approximately 270 cubiccentimeters with a width 16 of approximately 12 centimeters, a height 18of approximately 10.1 centimeters, and a depth 20 of approximately 4.8centimeters.

The body 12 includes a tapered distal end 26 and a broad proximal rim28. The proximal rim 28 defining an opening into an interior 32 of thebody 12. The body 12 has a substantially hollow interior 32 having aplurality of baffles 24. The body 12 includes, for example, 7 baffles 24that are approximately parallel to one another and span the width 16 ofthe implant 10. The baffles may, for example have a thickness of 2millimeters. The baffles 22 initiate on the interior surface of theinterior 32 at the distal side of the body 12 and extend towards theproximal rim 28. In order to allow room for the folds of the vascularbed and fat cell matrix, all or a portion of the baffles 24 do notextend completely to the proximal rim 28. Stated alternatively, thebaffles 24 are recessed within the interior 32 of the body 12 relativeto the rim 28.

As shown in FIG. 3B, in certain embodiments of the present invention,the body 12 includes perforations 30 that serve to facilitate fluidtransfer through the implant 10. The perforations 30 may be evenlydispersed over or across body 12 and/or may be dispersed relative to theposition of the baffles 24 or other structural feature(s). In FIG. 3B,the perforations 30 are shown as lines dispersed across the body 12.

With reference to FIG. 4 base 14 is substantially solid and includes aproximal side 34, a distal side 36, and a plurality of fins 38. The base14 may further employ a recess 40 around all or a portion of theperiphery of the distal side 36 of the base 14. The recess 40 provides asurface that is complementary to the proximal rim 28 of the body 12. Thebase includes, for example 6 fins 38 that initiate in the distal side 36of the base 14 and extend outward distally from the distal side 36 ofthe base 14. The fins 38 have a rounded profile when viewed incross-section, such as shown in FIG. 4. The fins 38 of the base 14 areapproximately parallel to one another and span the width 16 of the body12. The fins 38 are spaced relative to one another and to the height 18of the implant 10 so as to insert between the baffles 24 of the body 12when the body 12 and the base 14 are mated or brought together to formthe implant 10.

FIG. 6 shows a partial cut-away view of the body 12 mated to the base 14with the vascular bed 5 interposed between the baffles 24 of the body 12and the fins 38 of the base 14. As shown in FIGS. 3B, 5 and 6, the body12 further comprises aperture 42. Aperture 42 is formed by a notch orrecess in the proximal rim 28 and the recess 40 of the base 14. Theaperture serves as a port through which the vascular bed 5, and thus thecirculatory network of the vascular bed 5, may be enter and exit theimplant 10. While the aperture 42 is shown as being positioned at abottom portion of the implant, it is contemplated that the aperture 42may be positioned at alternative locations and that more than oneaperture 42 may be employed in an implant 10.

Formed within the body 12 and base 14, proximate an outer periphery ofthe body 12 and base 16 are suture points 22. The suture points 22 ofthe body 12 are positioned complementary to the suture points 22 formedwithin the base 14. The suture points 22 may comprise holes through thebody 12 and base 14 or may comprise regions of the body 12 and base 14that are thinner than the surrounding structure. The suture points 22allow for the easy attachment of the body 12 to the base 14 using knownsuturing methods.

With reference to FIGS. 7-16, in another embodiment of the presentinvention, the implant 100 is similar to the above described implant 10with the following exceptions. The implant 100 has, for example, avolume of approximately 300 cubic centimeters with a width 16 ofapproximately 12 centimeters, a height 18 of approximately 11centimeters, and a depth 20 of approximately 5.2 centimeters.

The proximal rim 128 of the body 112 of the implant 100 is irregularlyformed such that the proximal rim 128 follows the contour of a humanchest. For example, the rim 128 is formed such that it is not planarwhen viewed in cross-section, such as in FIG. 10. FIG. 10 shows that theleft side of the rim 128 from an angle 116 of approximately 5 degreesbeyond a planar line 118 drawn through a midpoint of the body 120 shownin FIGS. 9A and 9B. In this manner the rim 128 wraps around the contourof the chest of the patient more so than a planar rim 28. Furthermore,as shown in FIG. 10A, the body 112 employs a rectangular aperture 142that has a width 144 of approximately 4 centimeters and a depth 14 ofapproximately 1.5 centimeters. As shown in FIG. 9B, in an alternativeembodiment, the body 112 employs a rounded or arched aperture 142.Proximate the aperture 142, the body 112 employs one or more holes 148through which the vascular bed 5 may be secured to the body 112 by, forexample, suturing the vascular bed 5 to the body 112.

With reference to FIGS. 7, 9, 14, and 15, body 112 further employs ports149 through which injections into or extractions out from the implant100 are made. For example, the ports 149 may comprise a plurality ofholes or perforations located proximate the distal end 126 of the body112. The ports 149 may be used to, for example, inject additional fattissue matrix, nutrients, or pharmaceuticals into the implant 100 afterthe implant 100 has been implanted. In order to assist the physician orother caregiver in locating the ports 149, the ports 149 are positionedproximate a marker 150. The marker 150 may, for example, have anelevated form such as a nipple.

As shown in FIGS. 10, 14, and 15, the body 112 of the implant 100employs only two baffles 124. Also of note is that the baffles 124 arerecessed further within the interior 132 of the body 112 than thebaffles 24 of the body 12. These features of the implant 100 mayadvantageously provide increased space for the vascular bed 5 and fattissue matrix within the implant 100.

As shown in FIGS. 11-16, the base 114 employs 2 fins 138. The fins 138initiate in the distal side 138 of the base 114 and extend outward suchas the fins 38 described above for implant 10, however, the fins 138have a truncated, flat profile when viewed in cross-section, such asshown in FIGS. 11, 13, and 15.

With reference to FIGS. 17-20, in another embodiment of the presentinvention, the implant 200 is similar to the above described implant 10and 100 with the following exceptions. The implant 200 employs a body212 that includes baffles 224 that are slotted or otherwise non-solid inform.

In addition, implant 200 employs a base 214 that has an annular forminstead of the solid forms described above with respect to the bases 14and 114. The base 214 includes two fins 238 that initiate from thedistal side 238 of the base 114, however, given the annular form of thebase 214, i.e. the absence of material in the central portion of thedistal side 236 of the base 214, the fins 238 initiate from the distalside 236 only at a left and right side 152 of the base 214. As shown inFIG. 19, the fins 238 employ an arched or rounded distal side 248 andproximal side 250. As shown in FIG. 20, the fins 238 further employ atapered profile in which the proximal sides 250 of the fins 228 arethicker than the distal sides 248. As apparent from FIG. 18 the fins 238are also tapered across their width. Stated alternatively, the fins 238are thicker at the right and left sides 252 than the mid-portions 254.Finally, in contrast to the recess 40 of base 14, as shown in FIG. 18,base 214 employs an elevation. When the base 214 and the body 212 aremated, the elevation extends around an outside periphery of the body 212and serves to align and stabilize the mated base 214 to the body 212.

The implants 10, 100, and 200 according to the present invention may beformed of a single or a combination of bioasorbable material. Thevarious components of the implants 10, 100, and 200, e.g. the body,baffles, base, and fins, may be formed of the same or differentbioasorbable material. In certain embodiments, the various components ofthe implants 10, 100, and 200 are formed by injection molding techniquesknown in the art. Following injection molding, the components of theimplants are subjected to gamma irradiation for sterilization.

Exemplary bioabsorbable polymers that may be employed to form implantsaccording to the present invention include, but are not limited to,polylactic acid (PLA), polyglycolic acid (PGA), and mixtures thereof. Byutilizing polyglycolide and poly(l-lactide) as starting materials, asshown in FIG. 21, it is possible to co-polymerize the two monomers toextend the range of homopolymer properties.

These polymers are medical grade materials with excellent safetyprofiles, used in a wide range of medical devices, and are produced, forexample by Boehringer Ingelheim Resomer of Ridgefield, Conn. Thesepolymers degrade through non-enzymatic hydrolysis of the ester bonds.This degradation occurs as follows: (1) water penetrates the implant,attacking the chemical bonds and breaking the polymer chains(hydrolysis); (2) hydrolysis converts the long chains into non-toxicnatural metabolites (lactic acid and glycolic acid); (3) these moleculesare metabolized by the liver into CO₂ and H₂O and released through thelungs (Middleton J., Tipton A., Synthetic Biodegradable Polymers asMedical Implants. In: Medical Plastics and Biomaterials, 1998; thecontents of which are herein incorporated by reference).

Table 1 below summarizes the material properties of three co-polymersthat may be employed to form the implants of the present invention.

TABLE 1 Material Physical Properties Stress Modulus of Inherent at load,Elasticity, Bioresorbable Polymer Viscosity MPa MPaPoly(L-lactide-co-D,L-lactide) 70:30 3.8 73 432Poly(L-lactide-co-glycolide) 85:15 6.0 87 424Poly(L-lactide-co-glycolide) 82:18 2.1  87*  424*

The inherent viscosity also referred to as intrinsic viscosity or i.v.,is provided in deciliters per grams as 0.1 percent in CHCl₃, at 25degrees Celsius. It is also noted that the physical properties of the82:18 polymer are comparable to the published values of the 85:15polymer.

In order to access the physical properties of the bodies 12, 112, 212,static finite element analysis of the poly(L-lactide-co-glycolide) 85:15body 12 was performed. Static finite element analysis, FEA, is anumerical simulation technique used to calculate and visualize stressesand displacements of a material structure under load. A linear finiteelement simulation was performed on the body 12. A 145 pound load wasapplied to a small region of the distal end of body 12 of the model. Thefollowing material properties were used for the analysis:

Modulus of Tensile Modulus, Elasticity, Bioresorbable Polymer MPa MPaPoly(L-lactide-co-glycolide) 85:15 87 (12618 psi) 424 (61496 psi)

The maximum stress developed for the 145 pound load condition was 4,565pounds per square inch, psi. This value is well below the tensilestrength 12,618 psi of the material. Accordingly, the body should beoperable to preserve the shape of the breast against gravity and thepressure of overlying post-mastectomy skin. 145 pounds represents theexpected stress delivered upon the body 12 when the patient weighing upto 300 pounds lies prone, putting her mid-body weight on the implant 10.In general, most morbidly obese women are not candidates for breastreconstruction. FIG. 22 shows the FEA mesh applied to the model body 12,and FIG. 23 shows the results of the FEA.

Turning next to a method of use for the above described implants, FIG.24 illustrates a generalized flow-diagram of the steps employed in amethod 500 for using the bioabsorbable implants according to the presentinvention. The method 500 comprises a first step 510 in which fat isharvested from the patient by liposuction. Step 520 includes theidentification and isolation of the vascular bed 5, for example thenative omentum, within the chest defect of the patient by, for example,formation of a subcutaneous tunnel. Other sources of the vascular bed 5include the rectus abdominis muscle, latissimus muscle, external obliquemuscle, or serratus anterior muscle.

Next, the method 500 comprises step 530 in which the implant isassembled within the patient at the location of the chest defect thatresulted from the mastectomy. The step 30 includes packing the isolatedomentum inside the implant along with the fat tissue matrix, andsuturing the implant body to the implant base by utilizing knownsuturing methods and the suture points 22 formed within the body andbase of the implant. In order to maintain blood flow into and out fromthe assembled implant, a portion of the vascular bed 5 containingarterial and venous vasculature is placed though the aperture 42, 142,or 242 and maintained in vascular communication with the patient'snative circulatory network. Alternatively, the body and base of theimplant are sewn together with running sutures, leaving just enoughspace at the intersection of the body and base to allow blood flow intoand out from the vascular bed 5, but to prevent the fat tissue matrixfrom drifting or migrating out of the implant.

The following experimental examples were performed to further access thepresent invention.

EXAMPLE 1 Rat Study

Preliminary experiments were carried out in Sprague Dawley female ratsat approximately 3.5 months in age. Under general anesthesia, anincision was made in the inguinal region of the rat, and a portion ofthe rat's fat tissue was harvested. This fat tissue was manually mixedwith PuraMatrix (Becton Dickinson) in 10 percent sucrose solution. Thefat tissue matrix or mixture was placed inside a biodegradable meshpocket fabricated of Dexon mesh (U.S. Surgical Corporation), and securedshut with sutures. A midline laparotomy incision was made in the sameindividual rat, its omentum was identified and wrapped around the meshpocket, and secured with sutures. The rats tolerated the surgery well,and recovered without any complications. Four weeks later, the rats weresacrificed. The mesh pockets with fat inside were placed in paraffin,and Hematoxylin & Eosin, H&E, stained slides were generated.

The results demonstrated that the fat tissue inside the mesh pocketsurvived and was well vascularized. The thickness of the fat tissueranges from 2-6 millimeters. FIGS. 25 and 26 show well vascularized fattissue at 20× and 100× magnification, respectively.

In other rat-based experiments, the harvested fat tissue was placedimmediately adjacent to the omentum, and the mesh was wrapped outsideboth fat and omentum. H&E histochemistry demonstrated that both fat andomentum were incorporated into well vascularized fatty tissue withthickness ranging from 4-10 millimeters at four weeks.

EXAMPLE 2 Pig Study

For a pig study, a 9-month old Yucatan female pig weighing 50 kg wasused. Under general anesthesia, an incision was made in the subcutaneousabdominal region of the pig, and a portion of the pig's fat tissue washarvested. A midline laparotomy incision was made, the omentumidentified, and placed inside the scaffold. The fat tissue matrix wasplaced inside the implant between the folds of the omental, and the baseand body of the implant was secured shut with sutures. The implantremained inside the pig's abdominal cavity, attached to the omentumblood supply. The laparotomy incision was closed with running sutures.

The pig was observed during recovery daily by veterinary staff andexhibited no signs of complications. Four weeks later, the pig wassacrificed. The time period of four weeks was chosen because it usuallytakes at least two weeks to develop histological evidence of fatnecrosis. The implant with omentum and fat inside was retrieved. In thebreast, fat necrosis may manifest as calcifications seen on mammograms.Therefore, the scaffold was x-rayed, and as shown in FIG. 27, no calciumwas observed. As shown in FIG. 28, grossly, it appeared that the new fatgrew to a layer as thick as 1.5 centimeters. No gross evidence of tissuenecrosis was observed when the implant was sectioned.

Subsequently, the tissue inside the implant was sectioned, preserved inparaffin, and H&E stained slides of approximately 5 micrometer weregenerated. Under the microscope, as shown in FIG. 29, no fat necrosisinside the implant was observed. We also performed histologicalexaminations of the pig omentum (outside the scaffold), liver, spleen,intestine, and skin. All of these tissues and organs exhibited no signof damage or toxicity under the microscope.

Although the invention has been described in terms of particularembodiments and applications, one of ordinary skill in the art, in lightof this teaching, can generate additional embodiments and modificationswithout departing from the spirit of or exceeding the scope of theclaimed invention. Accordingly, it is to be understood that the drawingsand descriptions herein are proffered by way of example to facilitatecomprehension of the invention and should not be construed to limit thescope thereof.

1. An implant comprising: a bioabsorbable body having a bowl-likeprofile including a tapered end, a rim defining an opening into aninterior of the body, and a plurality of baffles spanning across theinterior of the body, and a base having a boundary substantiallycomplementary to the rim of the body and a plurality of fins extendingoutward from the base; wherein when the rim of the body is mated withthe base the fins of the base extend into the interior of the body andbetween the baffles of the body.
 2. The implant of claim 1, wherein theimplant is a breast implant.
 3. The implant of claim 1, wherein the bodyfurther comprises a plurality of suture points.
 4. The implant of claim1, wherein the body comprises perforations.
 5. The implant of claim 1,wherein the rim of the body comprises a recess that forms an apertureinto the interior of the body when the body is mated with the base. 6.The implant of claim 1, wherein a distal edge of at least one fin isrounded.
 7. The implant of claim 1, wherein a proximal edge of at leastone fin is rounded.
 8. The implant of claim 1, wherein along a width ofat least one fin the thickness of the fin varies.
 9. The implant ofclaim 1, wherein the implant comprises a body having two baffles and abase having two fins.
 10. The implant of claim 1, wherein at least onebaffle is slotted.
 11. The implant of claim 1, wherein the implantcomprises a bioabsorbable polymer.
 12. The implant of claim 1, whereinthe implant comprises a co-polymer formed from at least glycolide andlactide.
 13. An implant comprising: a bioabsorbable body havingbreast-shaped form and an aperture; and a vascular bed a portion ofwhich is positioned within an interior of the body and a differentportion of which extends through said aperture.
 14. The implant of claim13, wherein the bioabsorbable body comprises a co-polymer formed from atleast glycolide and lactide.
 15. The implant of claim 13, wherein thebioabsorbable body comprises a plurality of apertures.
 16. The implantof claim 13, wherein the interior of the body comprises a fat tissuematrix.
 17. The implant of claim 13, wherein the interior of the bodycomprises a plurality of structures about which the vascular bed isfolded.
 18. The implant of the claim 13, wherein the portion of thevascular bed that extends through the apertures comprises an arterialstructure.
 19. A breast implant comprising: comprising a bioabsorbablebody and further comprising an annular base having a plurality ofelements spanning from one side to the base to another side of the base;and a body having the form of a human breast and a rim that mates withthe base.
 20. The breast implant of claim 19, wherein when the base ismated to the body the plurality of elements of the base are interposedbetween baffles within an interior of the body.